The use of DNA for immunizations represents a new approach to raising immune responses. In this project, studies address (i) the role of professional antigen presenting cells in the initiation of DNA-raised responses, (ii) parameters that determine whether a DNA-raised response will be biased towards Th1 or Th2 T-cell help, (iii) the role of germinal centers in DNA raised antibody responses, (iv) the cytolytic T-cells (CTL) raised by Th1[unreadable] and Th2[unreadable] DNA immunizations, and (v) the consequences of different types of DNA-raised T-help for challenge infections. Studies on antibody and antibody-mediated protection use DNAs expressing normal (membrane-bound) and secreted forms of the influenza H1 hemagglutinin glycoprotein and the A/PR/8/34 (H1N1) murine influenza virus model.